Therapeutic applications of mesenchymal stem cell-derived extracellular vesicles in pain management: A narrative review of emerging evidence and future directions

Pain remains a major clinical challenge because current therapies often have limited efficacy and substantial adverse effects. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as promising candidates with anti-inflammatory, immunomodulatory, and neuroprotective actions. Preclinical studies show that MSC-EVs alleviate inflammatory, neuropathic, and cancer-related pain by modulating immune responses and promoting neural repair, thereby reducing nociceptor sensitization. MSC-EVs also hold potential as drug-delivery vehicles and as biomarkers for pain diagnosis due to their stability and bioactive cargo (<i>e.g.</i>, microRNAs and proteins). This narrative review summarizes terminology, mechanisms, therapeutic applications, and translational challenges of MSC-EVs in pain management, emphasizing their capacity to reshape the treatment landscape. Despite hurdles in scalable manufacturing, dosing, and regulation, ongoing clinical investigations support their promise as a biologically driven strategy for pain therapy.